This NCRR shared instrumentation proposal seeks funding for the purchase of an Applied Biosystems/Sciex new 5th generation QSTAR Elite(r) quadrupole orthogonal time-of-flight mass spectrometer and associated Tempo (Eksigent) nanocapillary multidimensional liquid chromatography (MDLC) station. To complete this integrated LC MS/MS system, we are also asking for a nanospray ion source, as well as ProteinPilot 2.0 and MarkerView software packages. In brief, we propose to operate this integrated LC MS/MS almost exclusively for on-line separation and analysis of complex peptide (and protein) mixtures as part of large group of 24 NIH funded grants from 15 investigators who have significant needs in state-of-the-art proteomics. The most critical features of this new instrumentation will be to greatly improve on the number of tandem mass spectra that can be acquired (up to 7 MS/MS spectra/sec), overall sensitivity (low attomole), dynamic range (4 logs), mass range (5-40,000 m/z), collision energetics, ion transmission, and quantitation software features. The unique capabilities of this instrumentation will be directed at a large array of protein and proteomic applications where mass spectrometry is used for protein/peptide identification in complex mixtures, relative quantitation, as well as the determination of biologically important enzymatic and non-enzymatic posttranslational modifications, including protein phosphorylation, oxidative damage and nitrosylation, among others. Overall, the acquisition of this instrument will greatly improve the throughput, experimental design, and discovery rate of 16 projects that are examining key issues of human health, including aging, neurodegenerative disease, cancer, biomarker discovery, stroke and infectious diseases. [unreadable] [unreadable] The relevance of this new instrumentation to human health is significant, as 13 independent researchers at two institutions (Buck Institute and UCSF) will use this new technology to improve their ongoing studies in the basic biology of aging and age-related diseases, including Huntington's and Alzheimer's disease, Parkinson's disease, breast cancer, and stroke. In addition, a smaller group of four investigators at the Buck Institute, UCLA and University of Iowa, that are investigating pathogenic mechanisms in several human infectious diseases including tuberculosis, meningitis, genital ulcers, respiratory disease, tularemia, and otitis media. [unreadable] [unreadable] [unreadable] [unreadable]